Nociceptive pain is pain generated from nociceptors responding to stimuli by sending nerve signals to the spinal cord and brain. Such signals may be indicative of tissue irritation, impending injury, or actual injury, and are often characterized as aching and/or direct pains. Examples of conditions associated with nociceptive pain include bone fractures, burns, bumps, bruises, inflammation (from an infection or arthritic disorder), arthralgia, general myalgia and more specific myalgia caused by symptoms categorized generally as amplified musculoskeletal pain (AMP) syndrome.
Neuropathic pain is pain caused by damage or disease that affects the somatosensory system. Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but it is not necessary for such an injury to involve actual damage to the central nervous system. Nerves can be infiltrated or compressed by tumours, strangulated by scar tissue, or inflamed by infection. The pain is typically characterized by burning, lancinating, coldness or so-called pins-and-needles-type sensations. Persistent allodynia—pain resulting from a non-painful stimulus such as a light touch—is also a common characteristic of neuropathic pain. The pain itself may have continuous and/or episodic (paroxysmal) components, the having electric shock-like qualities. The pain may persist for months or years beyond the apparent healing of any damaged tissue. In these scenarios, such pain signals no longer represent an alarm about ongoing or impending injury, rather it is the alarm system itself that is malfunctioning. Common causes of painful peripheral neuropathies are herpes zoster, infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, immune mediated disorders and physical trauma to a nerve trunk. Neuropathic pain is also common in cases of cancer, either as a direct result of a cancer on peripheral nerves (for example through compression by a tumour), or as a side effect of chemotherapy radiation, injury or surgery.
In certain conditions, the pain may be caused by a complex mixture of nociceptive and neuropathic factors. For example, myofascial pain is understood to result from nociceptive input from muscles. It is, however, plausible that such abnormal muscle activity is itself the result of neuropathic conditions.
In both neuropathic and nociceptive disease types, neurons become unusually sensitive and develop spontaneous activity, abnormal excitability, and a heightened sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is known as “peripheral sensitization”. Localized delivery of anaesthetic can afford a method of desensitizing the aberrant stimuli.
Lidocaine (often referred to as lignocaine) is widely used as a local anaesthetic, and is commercially available in both an injectable form and as a transdermal patch. When compared with a systemic dose, transdermal delivery of local anaesthetics provides prolonged anaesthesia at the target site for pain suppression, and involves reduced plasma levels, hence a reduced potential toxicity.
However, in spite of the widespread use of lignocaine transdermal patches, there remains a need for improved transdermal anaesthetic formulations.
In addition, there remains a need for improved analgesic transdermal patch formulations to provide analgesia, in particular improved patches for the delivery of opioid analgesics.
There is also a need for transdermal formulations having good skin penetration properties. Moreover, there is a need for transdermal formulations of anaesthetic or analgesic agents that exhibit improved drug potency and having a longer duration of action for reducing the occurrence of breakthrough pain.
Aspects of the invention were devised with the foregoing in mind.